[Vasculotoxicity of Chemotherapy: Assessment оf Endothelial Dysfunction Biomarkers' Levels in Gastric Cancer Patients].
- 作者列表："Kirichenko YY","Belenkov YN","Privalova EV","Naymann YI","Gitel EP","Novikova OV","Ilgisonis IS
:Aim To evaluate dynamics of biomarkers for endothelial dysfunction (ED), including endothelin-1 (ET-1) and von Willebrand factor (VWF) in patients with stomach cancer (adenocarcinoma) before and after polychemotherapy (PCT); to compare these results with respective values in healthy volunteers and patients with cardiovascular diseases (CVD); to study correlations of the ED biomarkers with indexes of instrumental evaluation of endothelial dysfunction.Material and methods The study included 75 participants, including 25 healthy volunteers (control group), 25 patients with documented CVDs (arterial hypertension + ischemic heart disease), and 25 patients of the main group with histologically documented stage II-IV stomach cancer (adenocarcinoma) who received different courses of PCT with platinum-based agents (oxaliplatin, cisplatin) and fluoropyrimidines (5 fluorouracil, capecitabin). Laboratory measurement of ED biomarkers, computerized nailfold video capillaroscopy (CNVC), and finger laser photoplethysmography (PPG) (methods for noninvasive evaluation of vascular wall and ED), electrocardiography, 24-h ECG Holter monitoring, and echocardiography (EchoCG) were performed for all patients of the main group prior to PCT and within one months after the last course completion. This evaluation was performed once for healthy volunteers and patients of the CVD group upon inclusion into the study.Results In the main group, ET-1 levels were non-significantly lower than normal and did not change during the courses of antitumor treatment (0.95 [0.6; 1.4] and 0.94 [0.7; 1.4] pg /ml (р<0.9) before and after PCT, respectively). Statistically significant differences were found between the control group and oncological patients after the treatment (р<0.04). Levels of VWF remained within the normal range in all examined participants and did not significantly differ between study groups, including oncological patients before and after the specific treatment (р>0.05 for all comparisons). The correlation analysis detected significant correlations of ET-1 levels with functional disorders of microcirculation, ET-1 with the occlusion index (rs=0.56; p=0.005), ЕТ-1 with percentage of capillary restoration (PCR, rs= -0.72; p=0.018) and with the incidence rate of supraventricular extrasystole (rs=0.48; p=0.032).Conclusion The dynamics of ED biomarkers was studied for the first time in patients with stomach cancer receiving a specific antitumor therapy. Although no significant changes in ЕТ-1 and VWF were observed during the PCT (probably due to exhaustion of the endothelial system and a small patient sample), these indexes can be considered as early vasculotoxicity markers due to the presence of significant correlations with indexes of impaired endothelial function according to the results of instrumental evaluation.
: 目的评价胃癌 (腺癌) 患者多次化疗 (PCT) 前后内皮功能障碍 (ED) 包括endothelin-1 (ET-1) 和血管性血友病因子 (VWF) 的动态变化; 将这些结果与健康志愿者和心血管疾病 (CVD) 患者的各自值进行比较;研究血管内皮功能障碍评价指标与ED生物标志物的相关性。材料和方法该研究包括75名参与者，包括25名健康志愿者 (对照组)，25名记录有CVDs (动脉高血压 + 缺血性心脏病) 的患者，以及25名主要组的组织学记录有ii-iv期胃癌的患者(腺癌) 接受不同疗程的PCT联合铂类药物 (奥沙利铂，顺铂) 和氟嘧啶 (5-氟尿嘧啶，卡培他滨)。ED生物标记物的实验室测量、计算机化甲襞视频毛细血管镜 (CNVC) 和手指激光光电容积描记术 (PPG) (血管壁和ED的无创评估方法) 、心电图、24小时心电图动态心电图监测和超声心动图 (EchoCG)在PCT之前和最后一个疗程完成后一个月内，对主要组的所有患者进行了在纳入研究后，对健康志愿者和CVD组患者进行一次评估。结果在主要组中，ET-1水平非显著低于正常，并且在抗肿瘤治疗过程中没有变化 (0.95 [0.6; 1.4] 和0.94 [0.7; 1.4] pgpg /ml (р<0.9)分别在PCT之前和之后)。在对照组和治疗后的肿瘤患者之间发现统计学显著差异 (р<0.04)。在所有被检查的参与者中，VWF水平保持在正常范围内，并且在研究组之间没有显著差异，包括在特定治疗之前和之后的肿瘤患者 (对于所有比较，р>0.05)。相关分析发现ET-1水平与微循环功能障碍显著相关，与闭塞指数ET-1 (rs = 0.56; p = 0.005)，е т -1与毛细血管恢复百分比 (PCR，rs = -0.72; p = 0.018) 和室上性心搏停止发病率 (rs = 0.48);p = 0.032)。结论首次在接受特异性抗肿瘤治疗的胃癌患者中研究了ED生物标志物的动力学。虽然在PCT期间没有观察到 е т -1和VWF的显著变化 (可能是由于内皮系统的衰竭和少量患者样本)，但根据仪器评估的结果，由于与内皮功能受损的指标存在显著相关性，这些指标可以被认为是早期血管毒性标志物。
METHODS::We present the case of a 61-year-old woman with a large tumoral infiltration extending from the pelvis throughout the inferior vena cava inferior to the right atrium, protruding into the right ventricle and right ventricular outflow tract. She had been treated 10 years before for low-grade endometrial stromal sarcoma by hysterectomy and adnexectomy followed by hormone- and radio-therapy. Due to cancer recurrence, she underwent peritonectomy, appendectomy, and resection of terminal ileum.
METHODS:AIMS:Significant platelet activation after long stented coronary segments has been associated with periprocedural microvascular impairment and myonecrosis. In long lesions treated either with an everolimus-eluting bioresorbable vascular scaffold (BVS) or an everolimus-eluting stent (EES), we aimed to investigate (a) procedure-related microvascular impairment, and (b) the relationship of platelet activation with microvascular function and related myonecrosis. METHODS AND RESULTS:Patients (n=66) undergoing elective percutaneous coronary intervention (PCI) in long lesions were randomised 1:1 to either BVS or EES. The primary endpoint was the difference between groups in changes of pressure-derived corrected index of microvascular resistance (cIMR) after PCI. Periprocedural myonecrosis was assessed by high-sensitivity cardiac troponin T (hs-cTnT), platelet reactivity by high-sensitivity adenosine diphosphate (hs-ADP)-induced platelet reactivity with the Multiplate Analyzer. Post-dilatation was more frequent in the BVS group, with consequent longer procedure time. A significant difference was observed between the two groups in the primary endpoint of ΔcIMR (p=0.04). hs-ADP was not different between the groups at different time points. hs-cTnT significantly increased after PCI, without difference between the groups. CONCLUSIONS:In long lesions, BVS implantation is associated with significant acute reduction in IMR as compared with EES, with no significant interaction with platelet reactivity or periprocedural myonecrosis.
METHODS:BACKGROUND:Aortopulmonary window is an uncommon congenital heart disease, with untreated cases not surviving beyond childhood. However, very rarely it can present in adult patients with features of pulmonary hypertension. Clinically these patients cannot be differentiated from other more common conditions with left to right shunt. Transthoracic echocardiography if performed meticulously, can depict the defect in aortopulmonary septum. RESULTS:We report a case of large unrepaired aortopulmonary window in a 23 years old patient, diagnosed on transthoracic echocardiography.